Effects of age-dependent changes in cell size on endothelial cell growth

Abstract

Described herein are angiogenic stimulating compositions comprising ML141 or a derivative thereof and methods of use of said angiogenic stimulating compositions for the treatment or prevention of a disease or injury in a subject, preferably a human subject of at least 50 years of age.

We claim: 
     
       1. A method of stimulating angiogenesis in a subject in need thereof comprising the step of: administering to the subject a therapeutically effective amount of ML141, whereby angiogenesis in the subject is stimulated, wherein the therapeutically effective amount of ML141 is administered as a composition having a ML 141 concentration of 0.1 μM to less than 15 μM. 
     
     
       2. The method of  claim 1 , wherein the ML141 is administered by subcutaneous, intravenous, or intraperitoneal injection. 
     
     
       3. The method of  claim 1 , wherein ML141 is administered in a gel. 
     
     
       4. The method of  claim 1 , wherein prior to administration of ML 141 or the derivative thereof, the area of endothelial cells of the subject are at least 1.5 times larger than the area of endothelial cells from a subject less than 50 years of age. 
     
     
       5. The method of  claim 4 , wherein endothelial cell size is measured by a method comprising the steps of:
 obtaining an adipose tissue sample from the subject; 
 staining the adipose tissue with a stain specific for endothelial cells; and 
 measuring the area of the stained endothelial cells. 
 
     
     
       6. The method of  claim 5 , wherein the stain silver nitrate. 
     
     
       7. The method of  claim 1 , wherein prior to administration of ML141, the endothelial cells of the subject are at least 25% less dense than endothelial cells from a subject less than 50 years of age. 
     
     
       8. The method of  claim 7 , wherein endothelial cell density is measured by a method comprising the steps of:
 obtaining an adipose tissue sample from the subject; 
 staining the adipose tissue with a stain specific for endothelial cells; and 
 measuring the density of the stained endothelial cells. 
 
     
     
       9. The method of  claim 8 , wherein the stain is silver nitrate. 
     
     
       10. The method of  claim 1 , wherein the ML141 is administered as part of a pharmaceutical composition additionally comprising a carrier. 
     
     
       11. The method of  claim 1 , wherein the subject has previously been diagnosed with cardiovascular disease, Alzheimer's, osteoporosis, diabetes, age-related macular degeneration, or chronic obstructive pulmonary disease. 
     
     
       12. A method of stimulating angiogenesis in a subject comprising: obtaining an adipose tissue sample from the subject; staining the adipose tissue with a stain specific for endothelial cells; measuring the area of the stained endothelial cells; and administering to the subject a therapeutically effective amount of ML141 when the area of the endothelial cells is at least 1.5 times larger than the area of endothelial cells from a subject less than 50 years of age, whereby angiogenesis is stimulated, wherein the therapeutically effective amount of ML141 is administered as a composition having a ML 141 concentration of 0.1 μM to less than 15 μM. 
     
     
       13. The method of  claim 12 , wherein the stain is silver nitrate. 
     
     
       14. The method of  claim 12 , wherein the ML141 is administered by subcutaneous, intravenous, or intraperitoneal injection. 
     
     
       15. The method of  claim 12 , wherein the ML141 is administered with a population of endothelial cells. 
     
     
       16. The method of  claim 12 , wherein the ML141 is administered as part of a pharmaceutical composition additionally comprising a carrier. 
     
     
       17. The method of  claim 16 , wherein the carrier is a gel. 
     
     
       18. The method of  claim 12 , wherein the subject has previously been diagnosed with cardiovascular disease, Alzheimer's, osteoporosis, diabetes, age-related macular degeneration, or chronic obstructive pulmonary disease.